Your browser doesn't support javascript.
Antibody escape and cryptic cross-domain stabilization in the SARS-CoV-2 Omicron spike protein.
Javanmardi, Kamyab; Segall-Shapiro, Thomas H; Chou, Chia-Wei; Boutz, Daniel R; Olsen, Randall J; Xie, Xuping; Xia, Hongjie; Shi, Pei-Yong; Johnson, Charlie D; Annapareddy, Ankur; Weaver, Scott; Musser, James M; Ellington, Andrew D; Finkelstein, Ilya J; Gollihar, Jimmy D.
  • Javanmardi K; Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX, USA. Electronic address: kjavanmardi@utexas.edu.
  • Segall-Shapiro TH; Laboratory of Antibody Discovery and Accelerated Protein Therapeutics, Center for Infectious Diseases, Houston Methodist Research Institute and Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, TX, USA.
  • Chou CW; Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX, USA.
  • Boutz DR; Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX, USA; Laboratory of Antibody Discovery and Accelerated Protein Therapeutics, Center for Infectious Diseases, Houston Methodist Research Institute and Department of Pathology and Genomic Medicine, Houston Methodist Hos
  • Olsen RJ; Laboratory of Antibody Discovery and Accelerated Protein Therapeutics, Center for Infectious Diseases, Houston Methodist Research Institute and Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, TX, USA; Laboratory of Molecular and Translational Human Infectious Disea
  • Xie X; Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX, USA.
  • Xia H; Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX, USA.
  • Shi PY; Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX, USA.
  • Johnson CD; Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX, USA.
  • Annapareddy A; Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX, USA.
  • Weaver S; University of Texas Medical Branch, World Reference Center for Emerging Viruses and Arboviruses, Galveston, TX, USA.
  • Musser JM; Laboratory of Molecular and Translational Human Infectious Diseases Research, Center for Infectious Diseases, HMRI and Department of Pathology and Genomic Medicine, HMH, Houston, TX, USA; Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY, USA.
  • Ellington AD; Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX, USA; Center for Systems and Synthetic Biology, The University of Texas at Austin, Austin, TX, USA.
  • Finkelstein IJ; Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX, USA; Center for Systems and Synthetic Biology, The University of Texas at Austin, Austin, TX, USA. Electronic address: ilya@finkelsteinlab.org.
  • Gollihar JD; Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX, USA; Laboratory of Antibody Discovery and Accelerated Protein Therapeutics, Center for Infectious Diseases, Houston Methodist Research Institute and Department of Pathology and Genomic Medicine, Houston Methodist Hos
Cell Host Microbe ; 30(9): 1242-1254.e6, 2022 09 14.
Article in English | MEDLINE | ID: covidwho-2035852
ABSTRACT
The worldwide spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to the repeated emergence of variants of concern. For the Omicron variant, sub-lineages BA.1 and BA.2, respectively, contain 33 and 29 nonsynonymous and indel spike protein mutations. These amino acid substitutions and indels are implicated in increased transmissibility and enhanced immune evasion. By reverting individual spike mutations of BA.1 or BA.2, we characterize the molecular effects of the Omicron spike mutations on expression, ACE2 receptor affinity, and neutralizing antibody recognition. We identified key mutations enabling escape from neutralizing antibodies at a variety of epitopes. Stabilizing mutations in the N-terminal and S2 domains of the spike protein can compensate for destabilizing mutations in the receptor binding domain, enabling the record number of mutations in Omicron. Our results provide a comprehensive account of the mutational effects in the Omicron spike protein and illustrate previously uncharacterized mechanisms of host evasion.
Subject(s)
Keywords

Full text: Available Collection: International databases Database: MEDLINE Main subject: Spike Glycoprotein, Coronavirus / COVID-19 Type of study: Randomized controlled trials Topics: Variants Limits: Humans Language: English Journal: Cell Host Microbe Journal subject: Microbiology Year: 2022 Document Type: Article

Similar

MEDLINE

...
LILACS

LIS


Full text: Available Collection: International databases Database: MEDLINE Main subject: Spike Glycoprotein, Coronavirus / COVID-19 Type of study: Randomized controlled trials Topics: Variants Limits: Humans Language: English Journal: Cell Host Microbe Journal subject: Microbiology Year: 2022 Document Type: Article